OPALIN is a CNS-specific transmembrane sialylglycoprotein expressed exclusively in oligodendrocytes and enriched in myelin paranodal loops 1. The protein contains a short N-terminal extracellular domain with N- and O-linked glycans, a transmembrane domain, and a long intracellular C-terminal domain, with glycosylation critical for proper cell surface localization 1. OPALIN promotes oligodendrocyte terminal differentiation through transcriptional regulation involving Myt1 and CREB transcription factors that bind conserved enhancer elements in the first intron 2. These signaling pathways are activated by leukemia inhibitory factor and cAMP, linking OPALIN expression to oligodendrocyte differentiation cascades 2. Beyond myelination, OPALIN has emerging disease relevance as a biomarker in vascular dementia pathogenesis 3 and shows altered expression in stress-related conditions 4 and Parkinson's disease models 5. Notably, OPALIN protein turnover is regulated by 2-hydroxylated sphingolipids through lysosomal degradation pathways, with impaired turnover implicated in hereditary spastic paraplegia 35 pathogenesis 6. OPALIN also interacts with TRPV2, a receptor with altered expression in demyelination disorders 7.